9-(4-hydroxybutyl)adenine-5′-monophosphate triethylammonium salt | 1514901-04-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(4-hydroxybutyl)adenine-5′-monophosphate triethylammonium salt
• CAS: 1514901-04-2
• 化学式: C₆H₁₅N*C₉H₁₄N₅O₄P
• 分子量: 388.407
• InChiKey: IYGYKIBQLPOFFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  26.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  139.62
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  9-(4-hydroxybutyl)adenine-5′-monophosphate triethylammonium salt 在 2,2'-二硫二吡啶 、 NADase 、 magnesium sulfate 、 三苯基膦 、 manganese(ll) chloride 作用下， 以 formamide 、 二甲基亚砜 为溶剂， 生成 9-(4-Hydroxybutyl)adenine 5'-diphosphoribose
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a
• 作为产物：
  描述：

  6-chloro-9-(4-acetoxybutyl)purine 在 甲醇 、 磷酸三乙酯 、 氨 作用下， 反应 19.0h， 生成 9-(4-hydroxybutyl)adenine-5′-monophosphate triethylammonium salt
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a